In Drosophila melanogaster, the major loci of the Segregation Distortion (SD) system are located near the centromere of the second chromosome. When an SD bearing second chromosome is heterozygous with an SD sensitive chromosome in a male, the sperm containing the SD sensitive chromosome develops abnormally. An unknown (but apparently large) number of modifying genes, which enhance or suppress the SD effect, are located elsewhere in the genome. This project is health related in the sense that many developmental abnormalities are contributed to abnormal gene regulation. The SD effect has been of substantial research interest for over three decades because it offers opportunity for figuring out how spermiogenesis is regulated. The SD modifiers are almost certainly an integral part of this regulation process yet they have been largely ignored by other investigators. Current efforts to identify and to determine how these modifiers affect the SD effect will be completed by the end of the grant period. Modifiers will be searched for in both natural populations and laboratory stocks of fruit flies. Some may be induced by ionizing radiation. The proportion of SD bearing offspring from males heterozygous for SD and carrying a given modifier (or set of modifiers) will serve as an essay of modifier effect. Marker genes in well defined stocks will allow for the genetic manipulation necessary for making various combinations of SD and its modifiers and for mapping modifiers to their respective chromosomal positions. Where there is indication of a modifier effect associated with chromosome abnormality, the chromosomes will be examined cytologically. Interactions among loci will be analyzed to see if the new combinations fit current concepts concerning the mechanism of the distorting effect. The research student trainees will participate in all phases of the research effort. This includes development of stocks for testing, doing the tests, and analyzing the results afterward. Students are expected to give presentations on the work they have done.